11
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Podocytes Regulate Neutrophil Recruitment by Glomerular Endothelial Cells via IL-6–Mediated Crosstalk

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Stromal cells actively modulate the inflammatory process, in part by influencing the ability of neighboring endothelial cells to support the recruitment of circulating leukocytes. We hypothesized that podocytes influence the ability of glomerular endothelial cells (GEnCs) to recruit neutrophils during inflammation. To address this, human podocytes and human GEnCs were cultured on opposite sides of porous inserts and then treated with or without increasing concentrations of TNF-α prior to addition of neutrophils. The presence of podocytes significantly reduced neutrophil recruitment to GEnCs by up to 50% when cultures were treated with high-dose TNF-α (100 U/ml), when compared with GEnC monocultures. Importantly, this phenomenon was dependent on paracrine actions of soluble IL-6, predominantly released by podocytes. A similar response was absent when HUVECs were cocultured with podocytes, indicating a tissue-specific phenomenon. Suppressor of cytokine signaling 3 elicited the immunosuppressive actions of IL-6 in a process that disrupted the presentation of chemokines on GEnCs by altering the expression of the duffy Ag receptor for chemokines. Interestingly, suppressor of cytokine signaling 3 knockdown in GEnCs upregulated duffy Ag receptor for chemokines and CXCL5 expression, thereby restoring the neutrophil recruitment. In summary, these studies reveal that podocytes can negatively regulate neutrophil recruitment to inflamed GEnCs by modulating IL-6 signaling, identifying a potential novel anti-inflammatory role of IL-6 in renal glomeruli.

          Related collections

          Most cited references66

          • Record: found
          • Abstract: found
          • Article: not found

          Glomerular-specific alterations of VEGF-A expression lead to distinct congenital and acquired renal diseases.

          Kidney disease affects over 20 million people in the United States alone. Although the causes of renal failure are diverse, the glomerular filtration barrier is often the target of injury. Dysregulation of VEGF expression within the glomerulus has been demonstrated in a wide range of primary and acquired renal diseases, although the significance of these changes is unknown. In the glomerulus, VEGF-A is highly expressed in podocytes that make up a major portion of the barrier between the blood and urinary spaces. In this paper, we show that glomerular-selective deletion or overexpression of VEGF-A leads to glomerular disease in mice. Podocyte-specific heterozygosity for VEGF-A resulted in renal disease by 2.5 weeks of age, characterized by proteinuria and endotheliosis, the renal lesion seen in preeclampsia. Homozygous deletion of VEGF-A in glomeruli resulted in perinatal lethality. Mutant kidneys failed to develop a filtration barrier due to defects in endothelial cell migration, differentiation, and survival. In contrast, podocyte-specific overexpression of the VEGF-164 isoform led to a striking collapsing glomerulopathy, the lesion seen in HIV-associated nephropathy. Our data demonstrate that tight regulation of VEGF-A signaling is critical for establishment and maintenance of the glomerular filtration barrier and strongly supports a pivotal role for VEGF-A in renal disease.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Suppressors of cytokine signalling (SOCS) in the immune system.

            The suppressors of cytokine signalling (SOCS) are a family of intracellular proteins, several of which have emerged as key physiological regulators of cytokine responses, including those that regulate the immune system. The SOCS proteins seem to regulate signal transduction by combining direct inhibitory interactions with cytokine receptors and signalling proteins with a generic mechanism of targeting associated proteins for degradation. Evidence is emerging for the involvement of SOCS proteins in diseases of the human immune system, which raises the possibility that therapeutic strategies that are based on the manipulation of SOCS activity might be of clinical benefit.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Signal transduction and the control of gene expression.

              More than 2000 transcription factors are encoded in the human genome. Such proteins have often been classified according to common structural elements. But because transcription factors evolved in the service of biologic function, we propose an alternative grouping of eukaryotic transcription factors on the basis of characteristics that describe their roles within cellular regulatory circuits.
                Bookmark

                Author and article information

                Journal
                J Immunol
                J. Immunol
                jimmunol
                jimmunol
                JI
                The Journal of Immunology Author Choice
                AAI
                0022-1767
                1550-6606
                1 July 2014
                28 May 2014
                : 193
                : 1
                : 234-243
                Affiliations
                [* ]Centre for Translational Inflammation Research, School of Immunity and Infection, University of Birmingham, Birmingham B15 2TT, United Kingdom;
                []School of Immunity and Infection, College of Medical and Dental Sciences, University of Birmingham, Birmingham B15 2TT, United Kingdom;
                []Academic Renal Unit, Southmead Hospital, Bristol BS10 5NB, United Kingdom;
                [§ ]Wellcome Trust Clinical Research Facility, University Hospital Birmingham Foundation Trust, Birmingham B15 2TH, United Kingdom; and
                []Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham, Birmingham B15 2TT, United Kingdom
                Author notes
                Address correspondence and reprint requests to Dr. Sahithi Jyothsna Kuravi, Renal Immunobiology, Centre for Translational Inflammation Research, University of Birmingham Research Laboratories, Birmingham B15 2WD, U.K. E-mail address: s.j.panchagnula@ 123456bham.ac.uk
                Article
                ji_1300229
                10.4049/jimmunol.1300229
                4067868
                24872191
                30879e29-48d6-4b88-9ca5-43a521046f78
                Copyright © 2014 The Authors

                This is an open-access article distributed under the terms of the CC-BY 3.0 Unported license .

                History
                : 23 January 2013
                : 21 April 2014
                Page count
                Pages: 10
                Categories
                Immune Regulation

                Comments

                Comment on this article